Severe impairment of endothelial function with the HIV-1 protease inhibitor indinavir is not mediated by insulin resistance in healthy subjects

Michael P. Dubé, Jude Christopher Gorski, Changyu Shen

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Endothelial dysfunction may contribute to increased cardiovascular events among HIV-1-infected patients receiving antiretroviral therapy. The HIV-1 protease inhibitor indinavir causes both vascular dysfunction and insulin resistance, but the relationship between the two disturbances is not established. Endothelium-dependent vasodilation (EDV), insulin-mediated vasodilation (IMV), and whole body and leg glucose uptake during a euglycemic hyperinsulinemic clamp (40 mU/m2/min) were measured before and after four weeks of indinavir in nine healthy men. EDV fell from 270 ± 67% above basal to 124 ± 30% (P = 0.04) and IMV from 56 ± 14% above basal to 8 ± 8% (P = 0.001) with indinavir. During the clamp, arteriovenous glucose difference and leg glucose uptake were not significantly different after indinavir and whole-body glucose uptake was only modestly reduced (8.0 ± 0.8 vs. 7.2 ± 0.8 mg/kg/min, P = 0.04). The change in EDV did not correlate with the change in whole-body glucose uptake after indinavir (r = 0.21, P = 0.6). Despite marked impairment of endothelial function and IMV with indinavir, only modest, inconsistent reductions in measures of insulin-stimulated glucose uptake occurred. This suggests that indinavir's effects on glucose metabolism are not directly related to indinavir-associated endothelial dysfunction. Studies of the vascular effects of newer protease inhibitors are needed.

Original languageEnglish
Pages (from-to)15-22
Number of pages8
JournalCardiovascular Toxicology
Volume8
Issue number1
DOIs
StatePublished - Mar 2008

Fingerprint

Indinavir
HIV Protease Inhibitors
Protease Inhibitors
Insulin Resistance
Healthy Volunteers
Vasodilation
Insulin
Glucose
Endothelium
Clamping devices
Leg
Glucose Clamp Technique
Human immunodeficiency virus 1 p16 protease
Metabolism
Vascular Resistance
Blood Vessels
HIV-1

Keywords

  • Endothelial dysfunction
  • HIV-1 protease inhibitors
  • Indinavir
  • Insulin sensitivity

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine

Cite this

Severe impairment of endothelial function with the HIV-1 protease inhibitor indinavir is not mediated by insulin resistance in healthy subjects. / Dubé, Michael P.; Gorski, Jude Christopher; Shen, Changyu.

In: Cardiovascular Toxicology, Vol. 8, No. 1, 03.2008, p. 15-22.

Research output: Contribution to journalArticle

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